Improving Efficacy and Safety of Oral Iron Supplementation in HIV-infected Children by Providing Prebiotic Galacto-oligosaccharides As Adjunct Treatment: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Iron status: Serum Ferritin (ug/L) (SF)
研究概览
简要总结
The objectives of this randomized controlled trial in virally suppressed HIV-positive children with anemia and/or depleted iron stores are to determine the effect of prebiotic galacto-oligosaccharides (GOS) as adjunct treatment to 12 weeks of oral iron supplementation on:
- iron status measured by conventional iron status biomarkers,
- fractional absorption of iron (fraction of total body iron per day, measured as Kabs, the slope of 57Fe isotopic dilution) and mean total amount of iron absorbed each day (mg Fe/day, calculated as Kabs x mean total body iron),
- systemic and gut inflammation, as well as gut mucosal integrity,
- gut microbiome composition, and
- adverse effects and gastrointestinal side-effects.
详细描述
Iron deficiency anemia (IDA) in childhood can impair growth and cognition, as well as reduce school performance. Furthermore, anemia frequently complicates pediatric HIV infection and predicts disease progression and mortality. However, there is no international consensus on the treatment of ID and IDA in HIV-infected children, because of concerns around the efficacy and safety of oral iron supplements. Recent studies have suggested that oral iron supplements may increase gut inflammation in African children. This could be particularly detrimental in HIV-infected children, who may have gut immune activation, enteropathy and adverse shifts in the gut microbiome.
Previous stable iron isotope studies from the ETH Laboratory of Human Nutrition showed that the consumption of prebiotic galacto-oligosaccharides (GOS) together with supplemental doses of iron can increase iron absorption. In Kenyan infants, we further showed that the addition of GOS to an iron-containing micronutrient powder mitigated the adverse effects of iron on the gut microbiome.
Thus, we hypothesize that providing GOS as adjunct treatment to oral iron supplementation will improve efficacy (iron absorption and iron status), reduce systemic and gut inflammation, improve mucosal integrity, and mitigated iron-induced alterations in the gut microbiome, adverse events and gastrointestinal side-effects in virally suppressed HIV-infected children.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 10-15 years at baseline;
- •Mild to moderate micro- and normocytic anaemia defined as Hb ≥8.0 and <11.5 / 12 g/dL (children 10-11 / 12-15 years) plus mean corpuscular volume ≤91.5 fL and/or iron deficiency defined as ferritin <30 µg/L or sTfR >8.3 mg/L;
- •Body-Mass-Index-for-age Z-scores (BAZ) -3 to 2 SD of reference population;
- •HIV criteria: HIV RNA viral load <50 copies/mL (measured as part of routine care);
- •Willingness of caregiver to participate in the study;
- •Caregiver speaks English, Afrikaans or isiXhosa;
- •The informed consent form has been read and signed by the caregiver (or has been read out to the caregiver in case of illiteracy) plus assent needs to be obtained from the child;
- •Residence in the study area for the period of the study.
排除标准
- •Child received iron supplements or antibiotic treatment 3 months prior to study start;
- •Acute illness or other conditions that in the opinion of the PI or co-researchers would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol;
- •Participants taking part in other studies involving medical or physical interventions.
研究组 & 干预措施
50 mg oral iron as ferrous fumarate (FeFum) with 7.5 g galacto-oligosaccharides
干预措施: Galacto-oligosaccharides (Dietary Supplement)
50 mg oral iron as ferrous fumarate (FeFum) with 7.5 g maltodextrin
干预措施: Maltodextrin (Other)
50 mg oral iron as ferrous fumarate (FeFum) with 7.5 g maltodextrin
干预措施: Ferrous fumarate (Dietary Supplement)
50 mg oral iron as ferrous fumarate (FeFum) with 7.5 g galacto-oligosaccharides
干预措施: Ferrous fumarate (Dietary Supplement)
结局指标
主要结局
Iron status: Serum Ferritin (ug/L) (SF)
时间窗: 0, 6, 12 weeks
Change in SF concentrations over the study period of 12 weeks
Iron status: Soluble Transferrin Receptor (mg/L) (sTfR)
时间窗: 0, 6, 12 weeks
Change in sTfR concentrations over the study period of 12 weeks
Iron status: Transferrin saturation (%) (Tsat)
时间窗: 0, 6, 12 weeks
Change in Tsat concentrations over the study period of 12 weeks
Iron status: Hemoglobin (g/dL) (Hb)
时间窗: 0, 6, 12 weeks
Change in Hb concentrations over the study period of 12 weeks
Fractional iron absorption
时间窗: 0, 6, 12 weeks
Fractional absorption of iron will be determined by measuring Kabs, the slope of 57Fe isotopic dilution over the study period. From this value, mean total amount of iron absorbed each day (mg Fe/day, calculated as Kabs x mean total body iron) can be estimated.
次要结局
- Systemic inflammation: C-reactive protein (mg/L) (CRP)(0, 6, 12 weeks)
- Systemic inflammation: Alpha-1-acid glycoprotein (g/L) (AGP)(0, 6, 12 weeks)
- Hepcidin (nM)(0, 6, 12 weeks)
- Gut inflammation: Intestinal fatty acids binding protein (ng/ml) (IFABP)(0 and 12 weeks)
- Gut inflammation: Fecal calprotectin (µg/g)(0 and 12 weeks)
- Gut inflammation: Myeloperoxidase (µg /mL) (MPO)(0 and 12 weeks)
- Gut microbiome composition(0 and 12 weeks)
- Fecal pH(0 and 12 weeks)
- HIV viral load (copies/ml)(0 and 12 weeks)
- Gastrointestinal and respiratory symptoms(12 weeks)